GSBS Student Publications

Title

NOD congenic mice genetically protected from autoimmune diabetes remain resistant to transplantation tolerance induction

UMMS Affiliation

Graduate School of Biomedical Sciences; Program in Immunology and Virology; Department of Medicine, Diabetes Division; Department of Medicine, Division of Endocrinology and Metabolism

Date

1-24-2003

Document Type

Article

Medical Subject Headings

Animals; Antibodies, Monoclonal; Antibody Specificity; Blood Transfusion; CD40 Ligand; Diabetes Mellitus, Type 1; Genetic Predisposition to Disease; Graft Survival; Immunity, Natural; Mice; Mice, Inbred C57BL; Mice, Inbred NOD; Skin Transplantation; Time Factors; Transplantation Tolerance

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

The loss of self-tolerance leading to autoimmune type 1 diabetes in the NOD mouse model involves at least 19 genetic loci. In addition to their genetic defects in self-tolerance, NOD mice resist peripheral transplantation tolerance induced by costimulation blockade using donor-specific transfusion and anti-CD154 antibody. Hypothesizing that these two abnormalities might be related, we investigated whether they could be uncoupled through a genetic approach. Diabetes-resistant NOD and C57BL/6 stocks congenic for various reciprocally introduced Idd loci were assessed for their ability to be tolerized. Surprisingly, in NOD congenic mice that are almost completely protected from diabetes, costimulation blockade failed to prolong skin allograft survival. In reciprocal C57BL/6 congenic mice with NOD-derived Idd loci, skin allograft survival was readily prolonged by costimulation blockade. These data indicate that single or multiple combinations of evaluated Idd loci that dramatically reduce diabetes frequency do not correct resistance to peripheral transplantation tolerance induced by costimulation blockade. We suggest that mechanisms controlling autoimmunity and transplantation tolerance in NOD mice are not completely overlapping and are potentially distinct, or that the genetic threshold for normalizing the transplantation tolerance defect is higher than that for preventing autoimmune diabetes.

Rights and Permissions

Citation: Diabetes. 2003 Feb;52(2):321-6.

Related Resources

Link to article in PubMed

Journal Title

Diabetes

PubMed ID

12540603